Magnetization transfer is a mechanism which may be exploited to generate contrast in a magnetic resonance image. The magnetization transfer effect is observed in biological tissue through the preparation of proton spins by application of radio-frequency (RF) energy prior to data acquisition. This effect is representative of the structure of the material under study, and the magnitude of the effect depends primarily on two experimental parameters, the average power and the frequency offset of the applied RF. This proposal identifies a description of the behavior of the magnetization transfer effect over the practical range of offset frequencies, which is referred to as the Z- spectrum, as a tool to improve the specificity of the magnetic resonance examination. The proposed studies will provide a means of characterizing tissues which are different in structure but have similar appearances on magnetic resonance images. Included in the proposed work are examinations of brain tissues which differ in extent of myelination. Specifically, the Z-spectrum will be obtained in normal brain tissue, brain tissue in patients with clinically diagnosed multiple sclerosis, and in brain tissue of animals with experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The brain tissue of the EAE animals will be studied to investigate the correlation between magnetic resonance observations and histopathological examination of the diseased tissue. Two variants of this animal model will employed, one which produces monophasic EAE and the other which produces a chronic relapsing disease course. Both types exhibit inflammatory lesions as well as focal areas of demyelination. Models of magnetization transfer predict that the nature of the proton spin relaxation environments determines the characteristics of the magnetization transfer effect. Therefore, analysis of the S-spectrum information will be based upon determination of the characteristics parameters which define the exchange of magnetization between different relaxation environments. A three-site model based upon coupled Bloch equations will be employed for determination of the relaxation and exchange parameters corresponding to each tissue type under study. These studies will result in characterization of brain tissues with quantitive magnetization transfer analysis, contributing to the ability of the magnetic resonance examination of distinguish lesions not currently differentiable, as well as to evaluate disorders which compromise myelination.